The Receptor-Mediated Leukemogenesis Hypothesis states that slowly transforming retroviruses induce leukemias by binding to antigen-specific receptors on T and B cells, simultaneously infecting those cells and triggering through their antigen-specific receptors a mitogenic response. Continued proliferation would be via continued restimulation of the same receptor mitogen complex. In this series of experiments designed to test the receptor mediated leukemogenesis hypothesis, we propose to analyze in detail the virus binding sites on B cell lymphoma immunoglobulins, and on T cell lymphomas. In addition, an extensive analysis will be carried out to define the molecular structures on the intact virus and on isolated virion proteins recognized by B cell and by T cell retrovirus receptors. If the molecules are isolated, a search will be made for the amino acid sequence of the important regions of viral receptors, and recombinant DNA techniques will be used to isolate transcripts of messenger RNA in these cells coding for such receptor molecules. If such transcripts are obtained, a cDNA representative of those transcripts will be made, and the genomic organization and transcriptual activity of various cells during lymphomagenesis/leukemogenesis will be studied. This project proposes to analyze, therefore, one potential mechanism by which oncogenic viruses can cause malignant neoplasms. It is complementary and perhaps competitive with current molecular mechanisms for leukemogenesis in other retrovirus induced tumor systems. By combining immunological, protein chemical, and molecular genetic approaches, we hope to test critically the receptor mediated leukemogenesis hypothesis, and other oncogene hypotheses for the generation of leukemia. The receptor mediated leukemogenesis hypothesis, if correct, has implications for tumorigenesis in general.